O76090 (BEST1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Bestrophin-1

Alternative name(s):
TU15B
Vitelliform macular dystrophy protein 2

Gene names

Name:	BEST1
Synonyms:	VMD2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	585 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Forms calcium-sensitive chloride channels. Highly permeable to bicarbonate. Ref.3 Ref.7 Ref.8
Subunit structure	Tetramer or pentamers. May interact with PPP2CB and PPP2R1B By similarity.
Subcellular location	Cell membrane; Multi-pass membrane protein. Basolateral cell membrane Ref.9.
Tissue specificity	Predominantly expressed in the basolateral membrane of the retinal pigment epithelium.
Post-translational modification	Phosphorylated by PP2A By similarity.
Involvement in disease	Vitelliform macular dystrophy 2 (VMD2) [MIM:153700]: VMD2 is an autosomal dominant form of macular degeneration that usually begins in childhood or adolescence. VMD2 is characterized by typical 'egg-yolk' macular lesions due to abnormal accumulation of lipofuscin within and beneath the retinal pigment epithelium cells. Progression of the disease leads to destruction of the retinal pigment epithelium and vision loss. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.2 Ref.8 Ref.10 Ref.11 Ref.12 Ref.13 Ref.15 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.25 Ref.26 Retinitis pigmentosa 50 (RP50) [MIM:613194]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Adult-onset vitelliform macular dystrophy (AVMD) [MIM:608161]: A rare autosomal dominant disorder with incomplete penetrance and highly variable expression. Patients usually become symptomatic in the fourth or fifth decade of life with a protracted disease of decreased visual acuity. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12 Bestrophinopathy, autosomal recessive (ARB) [MIM:611809]: A retinopathy characterized by loss of central vision, an absent electro-oculogram light rise, and electroretinogram anomalies. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.24 Vitreoretinochoroidopathy, autosomal dominant (ADVIRC) [MIM:193220]: A disorder characterized by vitreoretinochoroidal dystrophy. The clinical presentation is variable. VRCP may be associated with cataract, nanophthalmos, microcornea, shallow anterior chamber, and glaucoma. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.23
Sequence similarities	Belongs to the bestrophin family.
Sequence caution	The sequence BAH12234.1 differs from that shown. Reason: Erroneous initiation. The sequence BAH13472.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Ion transport Sensory transduction Transport Vision
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Retinitis pigmentosa
Domain	Transmembrane Transmembrane helix
Ligand	Calcium Chloride
Molecular function	Chloride channel Ion channel
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	detection of light stimulus involved in visual perception Inferred from electronic annotation. Source: Compara regulation of calcium ion transport Inferred from electronic annotation. Source: Compara transepithelial chloride transport Inferred from direct assay PubMed 17003041. Source: HGNC visual perception Traceable author statement Ref.2. Source: ProtInc
Cellular_component	basolateral plasma membrane Inferred from direct assay PubMed 11050159Ref.9. Source: UniProtKB chloride channel complex Inferred from electronic annotation. Source: UniProtKB-KW cytosol Traceable author statement PubMed 17003041. Source: HGNC integral to membrane Traceable author statement PubMed 10737974. Source: ProtInc
Molecular_function	chloride channel activity Inferred from direct assay PubMed 17003041. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O76090-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 3 (identifier: O76090-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-60: Missing.
     581-585: DEAHS → SVLHLNQGHC...EDFLGPGEGR

Isoform 4 (identifier: O76090-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-60: Missing.
     290-316: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 585	585	Bestrophin-1		PRO_0000143114
Regions
	Topological domain	1 – 25	25	Cytoplasmic Potential
	Transmembrane	26 – 46	21	Helical; Potential
	Topological domain	47 – 70	24	Extracellular Potential
	Transmembrane	71 – 91	21	Helical; Potential
	Topological domain	92 – 178	87	Cytoplasmic Potential
	Transmembrane	179 – 199	21	Helical; Potential
	Topological domain	200 – 228	29	Extracellular Potential
	Intramembrane	229 – 249	21	Potential
	Topological domain	250 – 270	21	Extracellular Potential
	Transmembrane	271 – 291	21	Helical; Potential
	Topological domain	292 – 585	294	Cytoplasmic Potential
Natural variations
	Alternative sequence	1 – 60	60	Missing in isoform 3 and isoform 4.		VSP_008973
	Alternative sequence	290 – 316	27	Missing in isoform 4.		VSP_008975
	Alternative sequence	581 – 585	5	DEAHS → SVLHLNQGHCIALCPTPASL ALSLPFLHNFLGFHHCQSTL DLRPALAWGIYLATFTGILG KCSGPFLTSPWYHPEDFLGP GEGR in isoform 3.		VSP_008974
	Natural variant	3	1	I → T in VMD2. Ref.26		VAR_058273
	Natural variant	6	1	T → P in VMD2 and AVMD. Ref.2 Ref.26 Corresponds to variant rs28940275 [ dbSNP | Ensembl ].		VAR_000830
	Natural variant	6	1	T → R in VMD2.		VAR_017366
	Natural variant	9	1	V → A in VMD2.		VAR_000831
	Natural variant	9	1	V → M in VMD2. Corresponds to variant rs28940276 [ dbSNP | Ensembl ].		VAR_000832
	Natural variant	10	1	A → T in VMD2.		VAR_000833
	Natural variant	10	1	A → V in VMD2. Ref.11		VAR_010468
	Natural variant	11	1	N → I in VMD2. Ref.20		VAR_017367
	Natural variant	13	1	R → H in VMD2. Ref.10		VAR_010469
	Natural variant	16	1	S → F in VMD2. Ref.16		VAR_010470
	Natural variant	17	1	F → C in VMD2. Ref.16		VAR_010471
	Natural variant	21	1	L → V in VMD2.		VAR_000834
	Natural variant	24	1	W → C in VMD2.		VAR_000835
	Natural variant	25	1	R → Q in VMD2.		VAR_000836
	Natural variant	25	1	R → W in VMD2.		VAR_000837
	Natural variant	26	1	G → R in VMD2. Ref.20		VAR_017368
	Natural variant	27	1	S → R in VMD2.		VAR_000838
	Natural variant	29	1	Y → H in VMD2. Ref.20		VAR_017369
	Natural variant	30	1	K → R in VMD2.		VAR_017370
	Natural variant	41	1	L → P in VMD2 and ARB. Ref.20 Ref.24		VAR_017371
	Natural variant	47	1	R → H in AVMD. Corresponds to variant rs28940278 [ dbSNP | Ensembl ].		VAR_017372
	Natural variant	58	1	Q → L in VMD2.		VAR_000839
	Natural variant	67	1	L → V.		VAR_000840
	Natural variant	73	1	I → N in VMD2. Ref.16		VAR_010472
	Natural variant	80	1	F → L in VMD2.		VAR_017373
	Natural variant	82	1	L → V in VMD2. Ref.11 Ref.26		VAR_010473
	Natural variant	85	1	Y → H in VMD2; loss of cloride and bicarbonate anions conduction. Ref.2 Ref.8 Corresponds to variant rs28940274 [ dbSNP | Ensembl ].		VAR_000841
	Natural variant	86	1	V → M in ADVIRC. Ref.23		VAR_058274
	Natural variant	89	1	V → A in VMD2. Ref.17		VAR_017374
	Natural variant	91	1	T → I in VMD2.		VAR_017375
	Natural variant	92	1	R → C in VMD2; loss of cloride and bicarbonate anions conduction. Ref.8 Ref.11		VAR_010474
	Natural variant	92	1	R → H in VMD2. Ref.16		VAR_010475
	Natural variant	92	1	R → S in VMD2.		VAR_000842
	Natural variant	93	1	W → C in VMD2; loss of cloride and bicarbonate anions conduction. Ref.2 Ref.8 Ref.10 Corresponds to variant rs28940273 [ dbSNP | Ensembl ].		VAR_000843
	Natural variant	96	1	Q → H in VMD2. Ref.11		VAR_010476
	Natural variant	99	1	N → K in VMD2.		VAR_000844
	Natural variant	100	1	L → R in VMD2.		VAR_000845
	Natural variant	101	1	P → T in VMD2.		VAR_017376
	Natural variant	102	1	W → R in VMD2. Ref.20		VAR_017377
	Natural variant	104	1	D → E in VMD2.		VAR_000846
	Natural variant	104	1	D → H in VMD2. Ref.20		VAR_017378
	Natural variant	105	1	R → C in age-related macular degeneration. Ref.15		VAR_025731
	Natural variant	113	1	F → L in VMD2. Ref.22		VAR_025732
	Natural variant	119	1	E → Q in a sporadic case of concentric annular macular dystrophy. Corresponds to variant rs1805142 [ dbSNP | Ensembl ].		VAR_010477
	Natural variant	133	1	N → K in VMD2.		VAR_017379
	Natural variant	135	1	G → S in VMD2. Ref.11		VAR_010478
	Natural variant	140	1	L → R in VMD2.		VAR_017380
	Natural variant	140	1	L → V in RP50; causes protein mislocalization to the cytoplasm and reduction of channel activity. Ref.9		VAR_063169
	Natural variant	141	1	R → H in VMD2 and ARB; reduced whole-cell conductance. Ref.24		VAR_000847
	Natural variant	146	1	A → K in AVMD; sporadic; requires 2 nucleotide substitutions. Ref.12 Corresponds to variant rs1800995 [ dbSNP | Ensembl ].		VAR_010479
	Natural variant	152	1	P → A in ARB; reduced whole-cell conductance. Ref.24		VAR_043493
	Natural variant	195	1	A → V in VMD2.		VAR_017381
	Natural variant	201	1	I → T in VMD2. Ref.15		VAR_025733
	Natural variant	205	1	I → T in RP50; reduced channel activity. Ref.9		VAR_063170
	Natural variant	207	1	L → I in VMD2. Ref.15		VAR_025734
	Natural variant	209	1	S → N in VMD2.		VAR_000848
	Natural variant	216	1	T → I in a sporadic case of age-related macular degeneration.		VAR_010480
	Natural variant	218	1	R → C in VMD2. Ref.10 Ref.11 Ref.16 Ref.25		VAR_000849
	Natural variant	218	1	R → H in VMD2. Ref.16		VAR_010481
	Natural variant	218	1	R → Q in VMD2.		VAR_000850
	Natural variant	218	1	R → S in VMD2. Ref.11		VAR_000851
	Natural variant	221	1	C → W in VMD2. Ref.13		VAR_025735
	Natural variant	222	1	G → V in a family affected by Leber congenital amaurosis/VMD2. Ref.14		VAR_025736
	Natural variant	224	1	L → M in VMD2.		VAR_000852
	Natural variant	224	1	L → P in VMD2. Ref.15		VAR_025737
	Natural variant	227	1	Y → C in RP50. Ref.9		VAR_000853
	Natural variant	227	1	Y → N in VMD2. Ref.2 Ref.26 Corresponds to variant rs28941469 [ dbSNP | Ensembl ].		VAR_000854
	Natural variant	228	1	D → N in RP50; causes protein mislocalization to the cytoplasm. Ref.9		VAR_063171
	Natural variant	231	1	S → R in VMD2.		VAR_000855
	Natural variant	235	1	V → L in VMD2. Ref.16		VAR_010482
	Natural variant	235	1	V → M in VMD2.		VAR_000856
	Natural variant	236	1	Y → C in ADVIRC. Ref.23		VAR_058275
	Natural variant	237	1	T → R in VMD2.		VAR_000857
	Natural variant	239	1	V → M in ADVIRC. Ref.23		VAR_058276
	Natural variant	241	1	T → N in VMD2. Ref.20		VAR_025738
	Natural variant	242	1	V → M in VMD2; late-onset of visual disturbance. Ref.25		VAR_058277
	Natural variant	243	1	A → T in VMD2. Ref.15 Corresponds to variant rs28940570 [ dbSNP | Ensembl ].		VAR_025739
	Natural variant	243	1	A → V in VMD2 and AVMD. Ref.26 Corresponds to variant rs28940570 [ dbSNP | Ensembl ].		VAR_000858
	Natural variant	275	1	V → I in age-related macular degeneration. Ref.15		VAR_025740
	Natural variant	276	1	F → L in VMD2. Ref.15		VAR_025741
	Natural variant	293	1	Q → K in VMD2. Ref.11		VAR_010483
	Natural variant	294	1	L → V in VMD2. Ref.20		VAR_025742
	Natural variant	295	1	I → T in VMD2. Ref.18		VAR_025743
	Natural variant	295	1	Missing in VMD2.		VAR_000859
	Natural variant	296	1	N → H in VMD2. Ref.15		VAR_025744
	Natural variant	296	1	N → S in VMD2. Ref.16		VAR_010484
	Natural variant	297	1	P → A in VMD2.		VAR_000860
	Natural variant	297	1	P → S in VMD2. Ref.12 Ref.21 Corresponds to variant rs1805143 [ dbSNP | Ensembl ].		VAR_010485
	Natural variant	298	1	F → S in VMD2. Ref.20		VAR_025745
	Natural variant	299	1	G → A in VMD2. Ref.26		VAR_058313
	Natural variant	299	1	G → E in VMD2. Ref.2 Corresponds to variant rs28941468 [ dbSNP | Ensembl ].		VAR_000861
	Natural variant	300	1	E → D in VMD2. Ref.10 Ref.12 Ref.21 Corresponds to variant rs1805144 [ dbSNP | Ensembl ].		VAR_010486
	Natural variant	300	1	E → K in VMD2.		VAR_000862
	Natural variant	301	1	D → E in VMD2. Ref.10		VAR_000863
	Natural variant	301	1	D → N in VMD2.		VAR_000864
	Natural variant	302 – 304	3	Missing in VMD2.		VAR_058278
	Natural variant	302	1	D → G in VMD2. Ref.15		VAR_025746
	Natural variant	302	1	D → H in VMD2. Ref.19		VAR_025747
	Natural variant	302	1	D → V in VMD2. Ref.15		VAR_025748
	Natural variant	303	1	D → E in VMD2. Ref.19		VAR_025749
	Natural variant	305	1	F → S in VMD2.		VAR_000865
	Natural variant	306	1	E → D in VMD2. Ref.15		VAR_025750
	Natural variant	306	1	E → G in VMD2. Ref.15		VAR_025751
	Natural variant	307	1	T → A in VMD2. Ref.15		VAR_025752
	Natural variant	307	1	T → I in VMD2. Ref.10		VAR_010487
	Natural variant	308	1	N → S in VMD2. Ref.19		VAR_025753
	Natural variant	310	1	I → T in VMD2.		VAR_000866
	Natural variant	311	1	V → G in VMD2.		VAR_000867
	Natural variant	312	1	D → N in AVMD and ARB; causes protein mislocalization to the cytoplasm. Ref.9 Ref.24		VAR_000868
	Natural variant	317	1	V → M in ARB. Ref.24		VAR_043494
	Natural variant	325	1	M → T in ARB. Ref.24		VAR_043495
	Natural variant	357	1	A → V. Ref.5 Corresponds to variant rs17854138 [ dbSNP | Ensembl ].		VAR_043496
	Natural variant	525	1	E → A. Ref.12		VAR_010488
	Natural variant	557	1	E → K. Ref.12		VAR_010489
	Natural variant	561	1	T → A. Ref.12		VAR_010490
	Natural variant	567	1	L → F in a sporadic case of age-related macular degeneration; could be a rare polymorphism.		VAR_010491
	Natural variant	578	1	E → V. Corresponds to variant rs1800010 [ dbSNP | Ensembl ].		VAR_009278

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: D0629AAF65BA1ACD	FASTA	585	67,684
	10 20 30 40 50 60 MTITYTSQVA NARLGSFSRL LLCWRGSIYK LLYGEFLIFL LCYYIIRFIY RLALTEEQQL 70 80 90 100 110 120 MFEKLTLYCD SYIQLIPISF VLGFYVTLVV TRWWNQYENL PWPDRLMSLV SGFVEGKDEQ 130 140 150 160 170 180 GRLLRRTLIR YANLGNVLIL RSVSTAVYKR FPSAQHLVQA GFMTPAEHKQ LEKLSLPHNM 190 200 210 220 230 240 FWVPWVWFAN LSMKAWLGGR IRDPILLQSL LNEMNTLRTQ CGHLYAYDWI SIPLVYTQVV 250 260 270 280 290 300 TVAVYSFFLT CLVGRQFLNP AKAYPGHELD LVVPVFTFLQ FFFYVGWLKV AEQLINPFGE 310 320 330 340 350 360 DDDDFETNWI VDRNLQVSLL AVDEMHQDLP RMEPDMYWNK PEPQPPYTAA SAQFRRASFM 370 380 390 400 410 420 GSTFNISLNK EEMEFQPNQE DEEDAHAGII GRFLGLQSHD HHPPRANSRT KLLWPKRESL 430 440 450 460 470 480 LHEGLPKNHK AAKQNVRGQE DNKAWKLKAV DAFKSAPLYQ RPGYYSAPQT PLSPTPMFFP 490 500 510 520 530 540 LEPSAPSKLH SVTGIDTKDK SLKTVSSGAK KSFELLSESD GALMEHPEVS QVRRKTVEFN 550 560 570 580 LTDMPEIPEN HLKEPLEQSP TNIHTTLKDH MDPYWALENR DEAHS
	Isoform 3 [UniParc]. Checksum: 4E105E710FC438BE	FASTA	604	69,096
	10 20 30 40 50 60 MFEKLTLYCD SYIQLIPISF VLGFYVTLVV TRWWNQYENL PWPDRLMSLV SGFVEGKDEQ 70 80 90 100 110 120 GRLLRRTLIR YANLGNVLIL RSVSTAVYKR FPSAQHLVQA GFMTPAEHKQ LEKLSLPHNM 130 140 150 160 170 180 FWVPWVWFAN LSMKAWLGGR IRDPILLQSL LNEMNTLRTQ CGHLYAYDWI SIPLVYTQVV 190 200 210 220 230 240 TVAVYSFFLT CLVGRQFLNP AKAYPGHELD LVVPVFTFLQ FFFYVGWLKV AEQLINPFGE 250 260 270 280 290 300 DDDDFETNWI VDRNLQVSLL AVDEMHQDLP RMEPDMYWNK PEPQPPYTAA SAQFRRASFM 310 320 330 340 350 360 GSTFNISLNK EEMEFQPNQE DEEDAHAGII GRFLGLQSHD HHPPRANSRT KLLWPKRESL 370 380 390 400 410 420 LHEGLPKNHK AAKQNVRGQE DNKAWKLKAV DAFKSAPLYQ RPGYYSAPQT PLSPTPMFFP 430 440 450 460 470 480 LEPSAPSKLH SVTGIDTKDK SLKTVSSGAK KSFELLSESD GALMEHPEVS QVRRKTVEFN 490 500 510 520 530 540 LTDMPEIPEN HLKEPLEQSP TNIHTTLKDH MDPYWALENR SVLHLNQGHC IALCPTPASL 550 560 570 580 590 600 ALSLPFLHNF LGFHHCQSTL DLRPALAWGI YLATFTGILG KCSGPFLTSP WYHPEDFLGP GEGR
	Isoform 4 [UniParc]. Checksum: EB111B7121ADC566	FASTA	498	57,349
	10 20 30 40 50 60 MFEKLTLYCD SYIQLIPISF VLGFYVTLVV TRWWNQYENL PWPDRLMSLV SGFVEGKDEQ 70 80 90 100 110 120 GRLLRRTLIR YANLGNVLIL RSVSTAVYKR FPSAQHLVQA GFMTPAEHKQ LEKLSLPHNM 130 140 150 160 170 180 FWVPWVWFAN LSMKAWLGGR IRDPILLQSL LNEMNTLRTQ CGHLYAYDWI SIPLVYTQVV 190 200 210 220 230 240 TVAVYSFFLT CLVGRQFLNP AKAYPGHELD LVVPVFTFLQ FFFYVGWLKV SLLAVDEMHQ 250 260 270 280 290 300 DLPRMEPDMY WNKPEPQPPY TAASAQFRRA SFMGSTFNIS LNKEEMEFQP NQEDEEDAHA 310 320 330 340 350 360 GIIGRFLGLQ SHDHHPPRAN SRTKLLWPKR ESLLHEGLPK NHKAAKQNVR GQEDNKAWKL 370 380 390 400 410 420 KAVDAFKSAP LYQRPGYYSA PQTPLSPTPM FFPLEPSAPS KLHSVTGIDT KDKSLKTVSS 430 440 450 460 470 480 GAKKSFELLS ESDGALMEHP EVSQVRRKTV EFNLTDMPEI PENHLKEPLE QSPTNIHTTL 490 KDHMDPYWAL ENRDEAHS

References

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[1]	"Mutations in a novel gene, VMD2, encoding a protein of unknown properties cause juvenile-onset vitelliform macular dystrophy (Best's disease)." Marquardt A., Stoehr H., Passmore L.A., Kraemer F., Rivera A., Weber B.H.F. Hum. Mol. Genet. 7:1517-1525(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VMD2.
[2]	"Identification of the gene responsible for Best macular dystrophy." Petrukhin K., Koisti M.J., Bakall B., Li W., Xie G., Marknell T., Sandgren O., Forsman K., Holmgren G., Andreasson S., Vujic M., Bergen A.A.B., McGarty-Dugan V., Figueroa D., Austin C.P., Metzker M.L., Caskey C.T., Wadelius C. Nat. Genet. 19:241-247(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS VMD2 PRO-6; HIS-85; CYS-93; ASN-227 AND GLU-299.
[3]	"Structure-function analysis of the bestrophin family of anion channels." Tsunenari T., Sun H., Williams J., Cahill H., Smallwood P., Yau K.-W., Nathans J. J. Biol. Chem. 278:41114-41125(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TOPOLOGY.
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4), VARIANT VAL-357. Tissue: Brain.
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 52-585 (ISOFORM 1). Tissue: Amygdala, Subthalamic nucleus and Synovium.
[7]	"The vitelliform macular dystrophy protein defines a new family of chloride channels." Sun H., Tsunenari T., Yau K.-W., Nathans J. Proc. Natl. Acad. Sci. U.S.A. 99:4008-4013(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Bestrophin Cl- channels are highly permeable to HCO3-." Qu Z., Hartzell H.C. Am. J. Physiol. 294:C1371-C1377(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS VMD2 HIS-85; CYS-92 AND CYS-93.
[9]	"Missense mutations in a retinal pigment epithelium protein, bestrophin-1, cause retinitis pigmentosa." Davidson A.E., Millar I.D., Urquhart J.E., Burgess-Mullan R., Shweikh Y., Parry N., O'Sullivan J., Maher G.J., McKibbin M., Downes S.M., Lotery A.J., Jacobson S.G., Brown P.D., Black G.C., Manson F.D. Am. J. Hum. Genet. 85:581-592(2009) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, VARIANTS RP50 VAL-140; THR-205; CYS-227 AND ASN-228, CHARACTERIZATION OF VARIANTS RP50 VAL-140; THR-205 AND ASN-228, CHARACTERIZATION OF VARIANT ARB ASN-312.
[10]	"Bestrophin gene mutations in patients with Best vitelliform macular dystrophy." Caldwell G.M., Kakuk L.E., Griesinger I.B., Simpson S.A., Nowak N.J., Small K.W., Maumenee I.H., Rosenfeld P.J., Sieving P.A., Shows T.B., Ayyagari R. Genomics 58:98-101(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS VMD2 HIS-13; CYS-93; CYS-218; ASP-300; GLU-301 AND ILE-307.
[11]	"The mutation spectrum of the bestrophin protein -- functional implications." Bakall B., Marknell T., Ingvast S., Koisti M.J., Sandgren O., Li W., Bergen A.A.B., Andreasson S., Rosenberg T., Petrukhin K., Wadelius C. Hum. Genet. 104:383-389(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS VMD2 VAL-10; VAL-82; CYS-92; HIS-96; SER-135; CYS-218; SER-218 AND LYS-293.
[12]	"Evaluation of the Best disease gene in patients with age-related macular degeneration and other maculopathies." Allikmets R., Seddon J.M., Bernstein P.S., Hutchinson A., Atkinson A., Sharma S., Gerrard B., Li W., Metzker M.L., Wadelius C., Caskey C.T., Dean M., Petrukhin K. Hum. Genet. 104:449-453(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS VMD2 SER-297 AND ASP-300, VARIANT AVMD LYS-146, VARIANTS GLN-119; ILE-216; ALA-525; LYS-557; ALA-561 AND PHE-567.
[13]	"A novel spontaneous missense mutation in VMD2 gene is a cause of a Best macular dystrophy sporadic case." Palomba G., Rozzo C., Angius A., Pierrottet C.O., Orzalesi N., Pirastu M. Am. J. Ophthalmol. 129:260-262(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT VMD2 TRP-221.
[14]	"Mutation analysis of 3 genes in patients with Leber congenital amaurosis." Lotery A.J., Namperumalsamy P., Jacobson S.G., Weleber R.G., Fishman G.A., Musarella M.A., Hoyt C.S., Heon E., Levin A., Jan J., Lam B., Carr R.E., Franklin A., Radha S., Andorf J.L., Sheffield V.C., Stone E.M. Arch. Ophthalmol. 118:538-543(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT VAL-222.
[15]	"Allelic variation in the VMD2 gene in best disease and age-related macular degeneration." Lotery A.J., Munier F.L., Fishman G.A., Weleber R.G., Jacobson S.G., Affatigato L.M., Nichols B.E., Schorderet D.F., Sheffield V.C., Stone E.M. Invest. Ophthalmol. Vis. Sci. 41:1291-1296(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS AGE-RELATED MACULAR DEGENERATION CYS-105 AND ILE-275, VARIANTS VMD2 THR-201; ILE-207; PRO-224; THR-243; LEU-276; HIS-296; GLY-302; VAL-302; ASP-306; GLY-306 AND ALA-307.
[16]	"Identification of novel VMD2 gene mutations in patients with Best vitelliform macular dystrophy." Marchant D., Gogat K., Boutboul S., Pequignot M., Sternberg C., Dureau P., Roche O., Uteza Y., Hache J.C., Puech B., Puech V., Dumur V., Mouillon M., Munier F.L., Schorderet D.F., Marsac C., Dufier J.-L., Abitbol M. Hum. Mutat. 17:235-235(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS VMD2 PHE-16; CYS-17; ASN-73; HIS-92; CYS-218; HIS-218; LEU-235 AND SER-296.
[17]	"Best's vitelliform macular dystrophy caused by a new mutation (Val89Ala) in the VMD2 gene." Eksandh L., Bakall B., Bauer B., Wadelius C., Andreasson S. Ophthalmic Genet. 22:107-115(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT VMD2 ALA-89.
[18]	"Identification of a novel VMD2 mutation in Japanese patients with Best disease." Yanagi Y., Sekine H., Mori M. Ophthalmic Genet. 23:129-133(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT VMD2 THR-295.
[19]	"Use of denaturing HPLC and automated sequencing to screen the VMD2 gene for mutations associated with Best's vitelliform macular dystrophy." Marchant D., Gogat K., Dureau P., Sainton K., Sternberg C., Gadin S., Dollfus H., Brasseur G., Hache J.C., Dumur V., Puech V., Munier F.L., Schorderet D.F., Marsac C., Menasche M., Dufier J.-L., Abitbol M. Ophthalmic Genet. 23:167-174(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS VMD2 HIS-302; GLU-303 AND SER-308.
[20]	"Ten novel mutations in VMD2 associated with Best macular dystrophy (BMD)." Kraemer F., Mohr N., Kellner U., Rudolph G., Weber B.H.F. Hum. Mutat. 22:418-418(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS VMD2 ILE-11; ARG-26; HIS-29; PRO-41; ARG-102; HIS-104; ASN-241; VAL-294 AND SER-298.
[21]	"Phenotype and genotype correlations in two best families." Seddon J.M., Sharma S., Chong S., Hutchinson A., Allikmets R., Adelman R.A. Ophthalmology 110:1724-1731(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS VMD2 SER-297 AND ASP-300.
[22]	"Gene Symbol: VMD2. Disease: Best vitelliform macular dystrophy (VMD2)." Li Y., Wang G.L., Dong B. Hum. Genet. 114:608-608(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT VMD2 LEU-113.
[23]	"Mutations of VMD2 splicing regulators cause nanophthalmos and autosomal dominant vitreoretinochoroidopathy (ADVIRC)." Yardley J., Leroy B.P., Hart-Holden N., Lafaut B.A., Loeys B., Messiaen L.M., Perveen R., Reddy M.A., Bhattacharya S.S., Traboulsi E., Baralle D., De Laey J.-J., Puech B., Kestelyn P., Moore A.T., Manson F.D.C., Black G.C.M. Invest. Ophthalmol. Vis. Sci. 45:3683-3689(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ADVIRC MET-86; CYS-236 AND MET-239.
[24]	"Biallelic mutation of BEST1 causes a distinct retinopathy in humans." Burgess R., Millar I.D., Leroy B.P., Urquhart J.E., Fearon I.M., De Baere E., Brown P.D., Robson A.G., Wright G.A., Kestelyn P., Holder G.E., Webster A.R., Manson F.D.C., Black G.C.M. Am. J. Hum. Genet. 82:19-31(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ARB PRO-41; HIS-141; ALA-152; ASN-312; MET-317 AND THR-325, CHARACTERIZATION OF VARIANTS ARB HIS-141 AND ALA-152.
[25]	"Mutation analysis of the VMD2 gene in Thai families with Best macular dystrophy." Atchaneeyasakul L.O., Jinda W., Sakolsatayadorn N., Trinavarat A., Ruangvoravate N., Thanasombatskul N., Thongnoppakhun W., Limwongse C. Ophthalmic Genet. 29:139-144(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS VMD2 CYS-218 AND MET-242.
[26]	"Clinical and molecular genetic analysis of Best vitelliform macular dystrophy." Boon C.J.F., Theelen T., Hoefsloot E.H., van Schooneveld M.J., Keunen J.E.E., Cremers F.P.M., Klevering B.J., Hoyng C.B. Retina 29:835-847(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS VMD2 THR-3; PRO-6; VAL-82; ASN-227; VAL-243; ALA-299 AND 302-ASP--ASP-304 DEL.
+	Additional computationally mapped references.

Web resources

VMD2 mutation database

Mutations of the VMD2 gene

Retina International's Scientific Newsletter

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF073500 , AF073491, AF073492, AF073493, AF073494, AF073495, AF073496, AF073497, AF073498, AF073499 Genomic DNA. Translation: AAC64926.1. AF057169 mRNA. Translation: AAC64343.1. AF057170 mRNA. Translation: AAC64344.1. AF073501 mRNA. Translation: AAC33766.1. AY515704 mRNA. Translation: AAR99654.1. CH471076 Genomic DNA. Translation: EAW73982.1. CH471076 Genomic DNA. Translation: EAW73985.1. BC015220 mRNA. Translation: AAH15220.1. BC041664 mRNA. Translation: AAH41664.1. AK289681 mRNA. Translation: BAF82370.1. AK295998 mRNA. Translation: BAH12234.1. Different initiation. AK301392 mRNA. Translation: BAH13472.1. Different initiation.
IPI	IPI00181929. IPI00549560. IPI00550794.
RefSeq	NP_001132915.1. NM_001139443.1. NP_004174.1. NM_004183.3.
UniGene	Hs.524910. Hs.712676.
3D structure databases
ProteinModelPortal	O76090.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000301774.
Protein family/group databases
TCDB	1.A.46.1.1. anion channel-forming bestrophin family.
PTM databases
PhosphoSite	O76090.
Proteomic databases
PaxDb	O76090.
PRIDE	O76090.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000378042; ENSP00000367281; ENSG00000167995. ENST00000378043; ENSP00000367282; ENSG00000167995. ENST00000449131; ENSP00000399709; ENSG00000167995. ENST00000524926; ENSP00000432681; ENSG00000167995.
GeneID	7439.
KEGG	hsa:7439.
UCSC	uc001nsr.2. human. uc001nss.3. human. uc001nst.3. human.
Organism-specific databases
CTD	7439.
GeneCards	GC11P061717.
H-InvDB	HIX0036211.
HGNC	HGNC:12703. BEST1.
MIM	153700. phenotype. 193220. phenotype. 607854. gene. 608161. phenotype. 611809. phenotype. 613194. phenotype.
neXtProt	NX_O76090.
Orphanet	99000. Adult-onset foveomacular vitelliform dystrophy. 3086. Autosomal dominant vitreoretinochoroidopathy. 1243. Best disease. 263347. MRCS syndrome. 791. Retinitis pigmentosa. 139455. Retinopathy, Burgess-Black type.
PharmGKB	PA162377454.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG315004.
HOVERGEN	HBG044928.
InParanoid	O76090.
KO	K13878.
OMA	YHSAPQT.
OrthoDB	EOG44BB2B.
PhylomeDB	O76090.
Gene expression databases
ArrayExpress	O76090.
Bgee	O76090.
CleanEx	HS_BEST1.
Genevestigator	O76090.
GermOnline	ENSG00000167995. Homo sapiens.
Family and domain databases
InterPro	IPR000615. Bestrophin. IPR021134. Bestrophin/UPF0187. [Graphical view]
PANTHER	PTHR10736. PTHR10736. 1 hit.
Pfam	PF01062. Bestrophin. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	BEST1. human.
GenomeRNAi	7439.
NextBio	29132.
SOURCE	Search...

Entry information

Entry name

BEST1_HUMAN

Accession

Primary (citable) accession number: O76090
Secondary accession number(s): A8K0W6 , B7Z3J8, B7Z736, O75904, Q53YQ9, Q8IUR9, Q8IZ80

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	November 1, 1998
Last modified:	May 1, 2013
This is version 129 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.